Sickle Cell Disease

Question 1

Sickle Cell Disease: is a group of ________________ RBC disorders that most commonly affects the _______________ population. It results from a ________________ in the genes that encode hemoglobin.

Answer 1

inherited/genetic

African American

genetic mutation

autosomal recessive

Question 2

What are problems with the red blood cells in Sickle cell disease:

Answer 2

• shortened life span 10-20 days
• unable to carry oxygen, less oxygen delivered throughout areas of body
• rbcs sickle/stick together in blood vessels
• a lot of complications in response to lack of oxygen to the tissues

Question 3

class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 3

class:

Indications:

MOA:

Dosage forms:

Dosing:

Max dose:

Contraindications:

Warnings:

Side Effects:

Monitoring:

Pearls/Notes:

Drug-Drug/Food interactions:

Question 4

(HgbS) Hemoglobin S =

Answer 4

“sickle” shape, this causes RBCs to be rigid with a concave “sickle shape

Question 5

Sickled RBCs burst (hemolyze) after ____

Answer 5

10-20 days, which causes anemia and fatigue. Have a much shorter life span. The bone marrow can not keep up with this rate of turnover for replacing these red blood cells. Patient becomes anemic.

Question 6

normal RBCs have a lifespan of _____________

Answer 6

90-120 days

Question 7

Irregularly shaped red blood cells are unable to _________

Answer 7

transport/carry oxygen effectivity. They stick together & get stuck, blocking smaller blood vessels (vascular occlusion) and causing many complications.

Question 8

Symptoms of sickle cell disease develop _____________

Answer 8

2-3 months after birth. This is because a fetus and young infants have RBCs with fetal hemoglobin (HgbF), which blocks the sickling of RBCs. Fetal hemoglobin (HgbF) is protective.

Question 9

HgbF:

Answer 9

fetal hemoglobin

Question 10

HgbA:

Answer 10

normal adult hemoglobin

Question 11

HgbS:

Answer 11

sickle shaped hemoglobin

Question 12

Acute Complications of Sickle Cell Disease:

Answer 12

• vaso-occlusive crisis (VOC) also called Acute pain crisis
• Acute Chest Syndrome
• anemia
• cholecystitis
• infections
• stroke
  -priapism
• multiorgan failure
• spleen sequestration

Question 13

Chronic Complications of Sickle Cell Disease:

Answer 13

• chronic pain
• avascular necrosis (bone death)
• pulmonary hypertension*
• renal impairment
  -leg ulcers
• gallstones
• pregnancy complications
• retinopathy
• priapism

Question 14

vascular occlusion:

Answer 14

prevents oxygen from reaching the tissues, causing them to become ischemic. This can lead to different types of Sickle Cell Crisis.

Question 15

vaso-occlusive crisis (VOC) also called Acute pain crisis:

Answer 15

• most commonly occurs in lower back, legs, hips, abdomen, and chest
• can last for days or weeks
• if their is pain in the chest and evidence of a pulmonary infection, then this is considered “Acute Chest Syndrome” which is life threatening and can lead to death

Question 16

Due to the risk of acute stroke, females with Sickle Cell Disease SHOULD NOT use ___________

Answer 16

estrogen contraceptives. Only Progestin-only contraceptives, levonorgestrel intrauterine devices (IUDs) and barrier methods are preferred for contraception.

Question 17

A healthy spleen has several physiologic roles including:

Answer 17

• removal of old or damaged red blood cells
• aid in immune function, making and storing white blood cells
• clearing some types of bacterial pathogens from the body, particularly encapsulated organisms: Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis

Question 18

In Sickle Cell Disease, the spleen becomes fibrotic and shrinks in size due to repetitive sickling and infarctions. This causes functional ________

Answer 18

asplenia (decreased or absent spleen function)

Question 19

Patients with Sickle Cell disease are at an increased risk for ________. They require immunizations and __________

Answer 19

• serious infections
• prophylactic antibiotics

Question 20

Non drug treatment in Sickle Cell Disease:

Answer 20

Blood transfusions protect against many of the life threatening complications of SCD by providing RBCs with hemoglobin A.

Question 21

Stroke, acute chest syndrome and severe anemia are acute complications that warrant treatment with ________

Answer 21

blood transfusions

Question 22

When administering chronic monthly blood transfusions, the goal Hgb level should be no higher than _____________.

One of the risks of blood transfusions is ____________

Answer 22

10 g/dL post infusion

iron overload, which can lead to hemosiderosis (excess iron that impairs organ function)

Question 23

The Only Cure for Sickle Cell Disease is ___________

Answer 23

bone marrow transplantation

Question 24

Major drug classes used in SCD include:

• immunizations & antibiotics for __________
• analgesics for__________
  -chelation therapy _____________

Answer 24

• to reduce infection risk
• controlling pain
• manage iron overload from blood transfusions

Question 25

Droxia

class:
Indications:
MOA:
Dosage forms: capsule
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 25

hydroxyurea

Class:

Indications: Sickle cell disease to reduce the frequency of acute pain crisis, episodes of acute chest syndrome, and the need for blood transfusions. Is indicated for adults with > than or equal to 3 moderate to severe pain crisis in one year, patients with severe or recurrent acute chest syndrome, chronic symptomatic anemia or disability. Use in all children > 9 months of age regardless of disease severity.

MOA: is a disease-modifying drug that STIMULATES the production of HgbF (fetal hemoglobin).

Dosage forms:

Dosing:

*Use IBW or TBW, whichever is less, when calculating daily dose.
*Round doses up to the nearest capsule size.

Max dose:

Boxed Warnings: *Myelosuppression (decreased WBCs and platelets),
malignancy (leukemia, skin cancer)

Warnings:
*Avoid Live Vaccines! since drug causes suppression
*Fetal toxicity, avoid in pregnancy (teratogenic)
Increased risk of pancreatitis, hepatotoxicity and peripheral neuropathy when used with antiretroviral drugs (especially didanosine & stavudine).

Side Effects:
increased LFTs, uric acid, BUN and SCr; mouth ulcers, N/V/D, alopecia, low sperm count (males),

Monitoring:
*CBC with differential every 2-4 weeks during treatment initiation and titration, then every 2-3 months once a stable dose is achieved. If toxicity occurs (ANC < 2000/mm3, platelets < 80000/mm3) hold hydroxyurea until the bone marrow recovers, then restart at a dose 5mg/kg/day lower.

Pearls/Notes:
*Contraception required during treatment AND after discontinuation (6 months for females and 12 months for males)

*Hazardous drug- cytotoxic, special handling required - wear gloves when dispensing and wash hands before and after contact. Capsules Should NOT be opened.

*Folic acid Supplementation is recommended to prevent macrocytosis
*Clinical response can take 3-6 months

Sunscreen should be used due to increased risk of skin cancer

Drug-Drug/Food interactions:

• Do NOT Use with pimecrolimus, tacrolimus and other drugs that cause myelosuppression (clozapine, deferiprone, leflunomide, natalizumab, tofacitinib)

Question 26

Hydrea

class:
Indications:
MOA:
Dosage forms: capsule
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 26

hydroxyurea

Class:

Indications: Sickle cell disease to reduce the frequency of acute pain crisis, episodes of acute chest syndrome, and the need for blood transfusions. Is indicated for adults with > than or equal to 3 moderate to severe pain crisis in one year, patients with severe or recurrent acute chest syndrome, chronic symptomatic anemia or disability. Use in all children > 9 months of age regardless of disease severity.

MOA: is a disease-modifying drug that STIMULATES the production of HgbF (fetal hemoglobin).

Dosage forms:

Dosing:

*Use IBW or TBW, whichever is less, when calculating daily dose.
*Round doses up to the nearest capsule size.

Max dose:

Boxed Warnings: *Myelosuppression (decreased WBCs and platelets),
malignancy (leukemia, skin cancer)

Warnings:
*Avoid Live Vaccines! since drug causes suppression
*Fetal toxicity, avoid in pregnancy (teratogenic)
Increased risk of pancreatitis, hepatotoxicity and peripheral neuropathy when used with antiretroviral drugs (especially didanosine & stavudine).

Side Effects:
increased LFTs, uric acid, BUN and SCr; mouth ulcers, N/V/D, alopecia, low sperm count (males),

Monitoring:
*CBC with differential every 2-4 weeks during treatment initiation and titration, then every 2-3 months once a stable dose is achieved. If toxicity occurs (ANC < 2000/mm3, platelets < 80000/mm3) hold hydroxyurea until the bone marrow recovers, then restart at a dose 5mg/kg/day lower.

Pearls/Notes:
*Contraception required during treatment AND after discontinuation (6 months for females and 12 months for males)

*Hazardous drug- cytotoxic, special handling required - wear gloves when dispensing and wash hands before and after contact. Capsules Should NOT be opened.

*Folic acid Supplementation is recommended to prevent macrocytosis
*Clinical response can take 3-6 months

Sunscreen should be used due to increased risk of skin cancer

Drug-Drug/Food interactions:

• Do NOT Use with pimecrolimus, tacrolimus and other drugs that cause myelosuppression (clozapine, deferiprone, leflunomide, natalizumab, tofacitinib)

Question 27

Siklos

class:
Indications:
MOA:
Dosage forms: scored tablet
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 27

hydroxyurea

Class:

Indications: Sickle cell disease to reduce the frequency of acute pain crisis, episodes of acute chest syndrome, and the need for blood transfusions. Is indicated for adults with > than or equal to 3 moderate to severe pain crisis in one year, patients with severe or recurrent acute chest syndrome, chronic symptomatic anemia or disability. Use in all children > 9 months of age regardless of disease severity.

MOA: is a disease-modifying drug that STIMULATES the production of HgbF (fetal hemoglobin).

Dosage forms:

Dosing:

*Use IBW or TBW, whichever is less, when calculating daily dose.
*Round doses up to the nearest capsule size.

Max dose:

Boxed Warnings: *Myelosuppression (decreased WBCs and platelets),
malignancy (leukemia, skin cancer)

Warnings:
*Avoid Live Vaccines! since drug causes suppression
*Fetal toxicity, avoid in pregnancy (teratogenic)
Increased risk of pancreatitis, hepatotoxicity and peripheral neuropathy when used with antiretroviral drugs (especially didanosine & stavudine).

Side Effects:
increased LFTs, uric acid, BUN and SCr; mouth ulcers, N/V/D, alopecia, low sperm count (males),

Monitoring:
*CBC with differential every 2-4 weeks during treatment initiation and titration, then every 2-3 months once a stable dose is achieved. If toxicity occurs (ANC < 2000/mm3, platelets < 80000/mm3) hold hydroxyurea until the bone marrow recovers, then restart at a dose 5mg/kg/day lower.

Pearls/Notes:
*Contraception required during treatment AND after discontinuation (6 months for females and 12 months for males)

*Hazardous drug- cytotoxic, special handling required - wear gloves when dispensing and wash hands before and after contact. Capsules Should NOT be opened.

*Folic acid Supplementation is recommended to prevent macrocytosis
*Clinical response can take 3-6 months

Sunscreen should be used due to increased risk of skin cancer

Drug-Drug/Food interactions:

• Do NOT Use with pimecrolimus, tacrolimus and other drugs that cause myelosuppression (clozapine, deferiprone, leflunomide, natalizumab, tofacitinib)

Question 28

Endari

class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 28

L-glutamine

class:

Indications: FDA approved for adults and children > or = to 5 years old with Sickle Cell Disease.
- Is an amino acid shown to reduce acute complications of SCD (number of pain crises requiring parenteral analgesics, number and duration of hospitalizations and occurrence of acute chest syndrome).

MOA: Not fully understood, but it is thought to decrease oxidative stress, which can damage sickled RBCs.

Dosage forms: oral powder

Dosing:

• dosing is based on TBW

TBW < 30kg: 5 grams BID
TBW 30-65kg: 10 grams BID
TBW > 65kg: 15 grams BID

Max dose:

Contraindications:

Warnings:

Side Effects: constipation, flatulence, nausea, headache, pain (abdominal, extremities, back, chest), cough

Monitoring:

Pearls/Notes:
- Mix each dose in 8 oz of a cold or room temperature beverage (water, milk, or apple juice) OR 4-6oz of food (applesauce or yogurt); medication does not have to be completely dissolved prior to administration.
- better safety profile than hydroxyurea

Drug-Drug/Food interactions:

Question 29

Oxbryta

class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 29

voxelotor

class:

Indications: FDA approved drug for patients age 4 years old and older with Sickle Cell Disease

MOA: Works by inhibiting hemoglobin S (HgbS) polymerization, which is the cause of SCD.

Dosage forms: tablet

Dosing:
1.5 grams once daily
(decrease dose if taking strong CYP3A4 inhibitors)
(increase dose if taking strong CYP3A4 inducers)

Max dose:

Contraindications:

Warnings:
hypersensitivity reactions, lab test interference with measurement of Hgb subtypes (A, F, S) by HPLC

Side Effects:
headache, fatigue, abdominal pain, diarrhea, nausea

Monitoring:

Pearls/Notes:
- can be given with or without hydroxyurea
- swallow tablets whole- do not crush, chew or cut tablet

Drug-Drug/Food interactions:

Question 30

Adakveo

class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Answer 30

crizanlizumab

class:

Indications: a monoclonal antibody that is FDA approved to reduce the frequency of vaso-occlusive crisis in Sickle Cell Disease.

MOA: works by binding to and inhibiting P-selectin, which is involved in adhesion of sickled erythrocytes to vessels (causing vaso-occlusion).

Dosage forms: injection

Dosing:
5mg/kg IV every 2 weeks for 2 doses THEN 5mg/kg every 4 weeks

Max dose:

Contraindications:

Warnings: infusion-related reactions

Side Effects: nausea, arthralgias, fever

Monitoring:

Pearls/Notes:

Drug-Drug/Food interactions:

Question 31

What happens when the red blood cells sickle to another and get stuck in the blood vessels?

Answer 31

patients can experience vasoocclusive crises. “acute pain crises”

• this can occur in a number of different organs

Question 32

What are the functions of a healthy spleen? In someone without Sickle Cell Disease

Answer 32

• removes old and damaged red blood cells
• stores white blood cells and helps immune function
• clears bacteria from the body:
  
  • Streptococcus pneumoniae
  • Haemophilus influenzae
  • Neisseria meningitidis
    “Encapsulated bacteria”

Question 33

functional asplenia:

Answer 33

“Develops in someone with sickle cell disease early on within 1-2 months of having disease”

• red blood cell sickling causes infarctions (ischemic attacks) of the spleen
• the spleen shrinks and becomes fibrotic (no longer functions)
• patients are at increased risk for infections

“complete loss of function of the spleen due to some medical condition”

Question 34

Non-drug treatment for Sickle Cell Disease:

Answer 34

• Blood Transfusions (chronic monthly)
  Supply HgbA
  Maintain serum Hemoglobin < or = to 10g/dL
  Risk: iron overload (which can cause hemosiderosis)

IF MONEY NOT AN ISSUE, THEN
- bone marrow transplantation

Question 35

If someone with Sickle Cell Disease has a fever of 101.3 or greater then _________

Answer 35

should immediately seek medical attention. If an infection is possible then needs to be addressed quickly.

Question 36

With blood transfusions in sickle cell patients, we are not aiming for a normal Hgb!! Because of the risk of ____

narrow range for hemoglobin in a patient with sickle cell disease is _______________

Answer 36

iron overload & hemosiderosis

narrow range for hemoglobin in a patient with sickle cell disease is less than or equal to 10g/dL

Question 37

Drug treatment for Sickle cell disease:

Answer 37

Immunizations: “that target those 3 encapsulated organisms”

Routine Childhood Series
- Haemophilus influenzae type B (Hib)
- Pneumococcal conjugate (PCV13, Prevnar 13)

Additional Vaccines for functional asplenia:
- Meningococcal conjugate series + routine boosters
- Meningococcal serogroup B (Bexsero, Trumenba) “ at age 10 and older”
- Pneumococcal Vaccines - give one of the following: “at age 19 and older”
- PCV20 (Prevnar 20) x1 OR
- PCV15 (Vaxneuvance) x1dose then followed by PPSV23 (Peunomovax23) 8 weeks or more later.

Antibiotics:
Oral penicillin VK BID until age 5

Analgesics:
IV opioids for severe pain
(PCA patient-controlled analgesia common)

Question 38

How do we dose hydroxyurea?

Question 39

How do you calculate ANC?

Answer 39

neutrophils = Polys = SEGs = PMN polymorphular nuclear sites

Question 40

When should we stop hydroxyurea in someone?

Question 41

How do we dose L-glutamine?

Answer 41

TBW

Question 42

Chelation therapy we use in patients with Sickle Cell disease to _______

Answer 42

remove excess iron stores from the body due to chronic blood transfusions

Question 43

what is the antidote for iron toxicity?

Answer 43

Historically, deferoxamine an infusion for 8-12 hours

Now we have oral chelating drugs:
deferasirox (Exjade, Jadenu)
deferiprone (Ferriprox)